Daily Ards Research Analysis
Analyzed 3 papers and selected 3 impactful papers.
Summary
Analyzed 3 papers and selected 3 impactful articles.
Selected Articles
1. Targeting macrophage ferritin heavy chain mitigates ferroptosis and lung injury in experimental acute respiratory distress syndrome.
This translational study reports enrichment of ferritin subunits (FTH1/FTL) in serum, monocytes, and alveolar macrophages from ARDS patients, validated in a murine hyperoxia lung injury model, and shows that targeting myeloid FTH1 reduces ferroptosis and lung injury. The mechanism links extracellular ferritin, macrophage iron handling, ferroptotic cell death, and inflammation, identifying FTH1 as a potential therapeutic target.
Impact: Provides novel mechanistic evidence that myeloid FTH1 drives ferroptosis and lung injury in ARDS, with translational validation in human samples and animal models — a clear candidate for therapeutic development.
Clinical Implications: Identifies FTH1/ferritin axis as a potential target for interventions to reduce ferroptosis-driven lung injury in ARDS; supports development of FTH1-modulating therapies or iron/ferroptosis-directed treatments and biomarker studies of serum ferritin compartments in ARDS patients.
Key Findings
- FTH1 and FTL are enriched in serum, peripheral monocytes, and alveolar macrophages of ARDS patients and replicated in a murine hyperoxia model.
- Myeloid-specific deletion or inhibition of Fth1 reduced ferroptosis markers and attenuated lung injury in experimental models.
- Extracellular ferritin correlates with worsened outcomes, linking macrophage iron handling to inflammatory lung injury and suggesting FTH1 as a targetable mediator.
Methodological Strengths
- Integration of human patient samples (serum, monocytes, alveolar macrophages) with in vivo murine models for cross-species validation.
- Mechanistic experiments with myeloid-specific genetic manipulation of Fth1 and measurement of ferroptosis and lung injury endpoints.
Limitations
- Translational gap: therapeutic modulation of FTH1 in humans and safety of targeting macrophage iron handling remain untested.
- Extent of clinical sample size and heterogeneity not specified in abstract; degree to which circulating ferritin subfractions predict outcomes requires larger cohorts.
Future Directions: Develop and test FTH1-modulating agents or ferroptosis inhibitors in preclinical ARDS models, validate serum/extracellular ferritin subfractions as prognostic biomarkers in large ARDS cohorts, and assess safety of targeting macrophage iron handling in translational trials.
Ferritin, composed of heavy chain (FTH1) and light chain (FTL) subunits, is a key intracellular iron storage protein, but the origin and biological role of extracellular ferritin (ex-ferritin) remain poorly understood. Elevated serum ex-ferritin is associated with worse outcomes in acute respiratory distress syndrome (ARDS). Here, we show that both FTH1 and FTL are significantly enriched in the serum, blood monocytes, and alveolar macrophages (AM) of individuals with ARDS, findings we replicate in a murine hyperoxia-induced acute lung injury model. Myeloid-specific FTH1 (Fth1
2. Multidisciplinary telemedicine intervention for ICU recovery: the TelePORT feasibility randomized trial.
A two-site pilot randomized trial (n=91) evaluated a multidisciplinary telemedicine post-ICU recovery clinic for survivors of sepsis and/or ARDS. The intervention was feasible with high clinician fidelity and acceptable patient ratings, but attendance/engagement was modest and exploratory PICS outcomes at 6 months did not differ between groups.
Impact: Demonstrates feasibility and acceptability of a multidisciplinary telemedicine model for post-ICU recovery after ARDS/sepsis, providing an essential foundation for larger trials focused on engagement and equity.
Clinical Implications: Supports conducting larger randomized trials to test efficacy; clinicians and health systems can consider telemedicine recovery clinics as feasible but should plan strategies to improve patient engagement and include diverse populations before broad implementation.
Key Findings
- In this pilot RCT (n=91), telemedicine arm attendance was modest: 55% at 3 weeks and 42.5% at 3 months among eligible participants; 57.5% attended at least one visit.
- Clinician fidelity to the multidisciplinary telemedicine visits was high and participants reported favorable acceptability, appropriateness, and feasibility.
- Exploratory composite outcomes of PICS (cognitive, mental health, physical domains) at 6 months did not differ significantly between telemedicine and standard care groups.
Methodological Strengths
- Randomized controlled design with trial registration (NCT03926533) across academic and community centers.
- Multidisciplinary intervention with predefined feasibility outcomes and high clinician fidelity metrics.
Limitations
- Pilot sample size limited power to detect clinical effectiveness; substantial attrition/attendance issues reduced evaluable endpoints.
- Study population was demographically homogeneous (91% White among those assessed), limiting generalizability and equity conclusions.
Future Directions: Larger, adequately powered randomized trials should test clinical effectiveness on PICS outcomes, with strategies to increase engagement (e.g., outreach, tech support, flexible scheduling) and deliberate inclusion of underrepresented populations.
BACKGROUND: Survivors of critical illness commonly experience post-intensive care syndrome (PICS), including cognitive, mental health, physical, quality-of-life, and social impairments after discharge. Telemedicine may improve access to post-ICU recovery clinic care, but its feasibility and effect on recovery outcomes remain unclear. We evaluated the feasibility of a multidisciplinary telemedicine post-ICU recovery clinic and collecting 6-month outcome data.
METHODS: We conducted a two-site pilot feasibility randomized controlled trial at an academic medical center and regional community medical center in the southeastern United States. Adults admitted to medical or surgical ICUs with sepsis and/or acute respiratory distress syndrome were randomized 1:1 to telemedicine ICU recovery clinic visits or standard care. The intervention included two multidisciplinary visits at 3 weeks and 3 months after hospital discharge; participants accessed visits via a secure web-based personal health portal, where they videoconferenced simultaneously with an ICU clinician, pharmacist, and psychologist. Participants in the standard of care group received usual post-discharge care. Feasibility outcomes included enrollment, retention, attendance, clinician fidelity, and participant ratings of acceptability, appropriateness, and feasibility. Exploratory outcomes included cognitive, mental health (i.e., depression, anxiety, PTSD), and physical health (i.e., activities of daily living, independent activities of daily living) composite scores measured at 1 week and 6 months after hospital discharge.
RESULTS: Of 1,108 screened patients, 91 were randomized (telemedicine, n = 46; standard care, n = 45). Among 83 participants completing the 1-week assessment, median age was 56 years, 51% were male, and 91% were White. In the telemedicine arm, 23 participants (57.5%) attended at least one visit; attendance was 55% at 3 weeks and 42.5% at 3 months among eligible participants. Primary 6-month outcome assessment was completed by 31 participants in each group (67%). Clinician participation fidelity was high, and telemedicine attendees reported favorable acceptability, appropriateness, and feasibility ratings. Exploratory analyses of PICS composite outcomes did not differ significantly between groups.
CONCLUSION: A multidisciplinary telemedicine post-ICU recovery clinic and associated trial procedures were feasible, with high clinician fidelity and favorable participant ratings. Larger trials are needed to explore engagement strategies and evaluate effectiveness on long-term recovery outcomes, prioritizing inclusion of more diverse and historically underrepresented populations.
TRIAL REGISTRATION: NCT03926533 (posted 4/24/2019).
3. Superior mesenteric artery Doppler after first feed and its association with feed intolerance and necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study.
Prospective cohort of 50 VLBW neonates assessed SMA Doppler before and 60 minutes after first feed. While post-feed RI fell significantly, SMA Doppler parameters were not independently associated with time to full feeds after adjustment; RDS and hsPDA had stronger associations. SMA Doppler showed modest discrimination for feed intolerance and NEC but limited predictive value as standalone markers.
Impact: Provides prospective neonatal data suggesting SMA Doppler changes after first feed relate to feed intolerance but lack sufficient predictive power alone, highlighting the influence of systemic neonatal illnesses and clinical management.
Clinical Implications: Clinicians should not rely solely on single post-feed SMA Doppler measures to predict feed intolerance or NEC in VLBW infants; consider systemic diagnoses (RDS, hsPDA) and individualized feeding protocols. SMA Doppler may supplement but not replace clinical judgment or multifactorial risk models.
Key Findings
- Post-feed resistive index (RI) decreased significantly (median 0.76 to 0.68; P = .01) in VLBW neonates.
- After adjustment, SMA Doppler parameters were not independently associated with time to full enteral feeds; RDS and hsPDA were significant predictors.
- SMA Doppler showed modest discrimination for feed intolerance (AUC 0.69) and exploratory modest discrimination for NEC (AUC 0.72) but limited standalone predictive value.
Methodological Strengths
- Prospective cohort design with standardized pre- and post-feed Doppler protocol and adjustment for clinical confounders.
- Use of objective Doppler metrics and time-to-event analysis (Kaplan–Meier) for feeding progression.
Limitations
- Small sample size (n=50) limits statistical power, particularly for NEC outcomes which were infrequent.
- Single-center tertiary NICU setting and clinician-driven feeding management decisions may limit generalizability and introduce management-related confounding.
Future Directions: Larger multicenter prospective studies should test SMA Doppler as part of multivariable predictive models for feed intolerance/NEC and evaluate whether serial Doppler monitoring or combined biomarkers improve prediction over clinical variables alone.
To evaluate the association of superior mesenteric artery (SMA) Doppler parameters after the first feed with feed intolerance and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) neonates. This prospective cohort study was conducted in a tertiary neonatal intensive care unit from July 2024 to January 2025. VLBW neonates underwent SMA Doppler assessment before and 60 min after the first feed using standardized protocols. The primary outcome was time to full enteral feeds; secondary outcomes included feed intolerance, NEC, and sepsis. Fifty neonates were included. Post-feed resistive index (RI) decreased significantly (0.76-0.68; P = .01). On adjusted analysis, SMA Doppler parameters were not independently associated with time to full feeds, while respiratory distress syndrome (RDS) and hemodynamically significant patent ductus arteriosus (hsPDA) were significantly associated. Median time to full feeds was 9 days on Kaplan-Meier analysis. Neonates with feed intolerance had lower post-feed pulsatility index (PI) and RI, and a greater fall in RI. ROC analysis showed modest discrimination (AUC 0.69, 95% CI 0.53-0.84). Doppler differences in neonates with NEC were not statistically significant; an exploratory model showed modest discrimination (AUC 0.72, 95% CI 0.50-0.87). SMA Doppler parameters show possible association with feed intolerance and NEC but have limited predictive value as standalone markers. Feeding progression appeared to be more strongly influenced by systemic illnesses such as RDS, hsPDA, and by clinical management factors including feed withholding and individualized advancement decisions.